Neural stem cells offer a possible source of cells for cell replacement therapies for neuro-degenerative diseases or injury of the nervous system. Currently neural stem cells are limited in their use because after transplantation into the adult CNS they generate largely undifferentiated or glial progeny. The ability to direct what types of cells stem cells make is the long term objective of this proposal. Previous data from the lab shows that stem cells change during development, so that they produce fewer neurons and more glia. The first aim will be to analyse the gene expression changes that accompany this change in potential. Stem cells will be prospectively isolated from mouse forebrain at different embryonic ages by a novel technique recently developed in the lab. Representational difference analysis (RDA) will be carried out to obtain clones of genes that are differentially expressed at these ages. It is anticipated that differences will be obtained, given that this approach has recently been shown to be applicable to neural stem cells. In the second aim, expression of selected genes identified by RDA will be examined by in situ. Genes expressed in germinal zones and which are developmentally regulated will be ectopically expressed in forebrain progenitor cells in vitro and in vivo using retroviral vectors to test their influence on the types of neuronal and glial progeny generated.